The objective of this proposed research is to elucidate the role of the metabolic interconversions of vitamin K, vitamin K epoxide, and vitamin K hydroquinone in providing the active form of the vitamin required in the vitamin K-dependent carboxylation complex involved in the biosynthesis of blood clotting proteins and to elucidate the inhibitory role of the anticoagulant warfarin. The project is the result of observations that rat liver microsomes solubilized by treatment with potassium cholate retain vitamin K epoxide reductase and vitamin K-dependent carboxylase activities. Experiments are planned to purify vitamin K epoxide reductase, to determine by kinetic methods the relationship of the metabolic interconversions of vitamin K to its action in the carboxylation of precursor proteins, and to ascertain the mechanism of warfarin interference with these reactions.